The specific purpose of this proposal is to characterize the mitochondrial DNA defects predisposing to aminoglycoside ototoxicity, identify nuclear-encoded genes implicated in aminoglycoside sensitivity, study the biochemical effects of predisposing mutations in vitro, and determine the frequencies of predisposing mutations in the different ethnic groups present in the U.S. The GCRC has assisted in the identification of potential recruitment sources for aminoglycoside exposed individuals for the development of a control group.